title: CD49d expression and function on allergen-stimulated T cells from blood and airway.
abstract: The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Pacheco
authors.forename: M
authors.initials: M
authors.lastname: Tarkowski
authors.forename: J
authors.initials: J
authors.lastname: Klemm
authors.forename: L J
authors.initials: LJ
authors.lastname: Rosenwasser
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005353:Fibronectins; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D010446:Peptide Fragments; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000485:Allergens; D015703:Antigens, CD; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D006684:HLA-DR Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D010446:Peptide Fragments; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4